Progress Free Survival (PFS) and Overall Survival (OS)Phase 2NCT04393220
Combination of PD-1 and VEGFR-2 Blockade for Advanced Hepatocellular Carcinoma
A Phase 2 study testing Bevacizumab Injection and Nivolumab in people with Progress Free Survival (PFS) and Overall Survival (OS), run by Fuda Cancer Hospital, Guangzhou at 1 site in China.
Trial summary
The aie of this clinical study is the safety and efficacy of combination therapy for HCC patients. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Progress Free Survival (PFS) and Overall Survival (OS)
- What is being tested?
- Bevacizumab Injection and Nivolumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteChina
- Study dates
- 11 May 2020to 31 Aug 2021
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1. Age 18-70 (inclusive), male and female
- 2. HCC was diagnosed by histopathological examination or the guidelines for the diagnosis and treatment of primary liver cancer (2017 edition).
- 3. Stage B (intermediate) or stage C (advanced) HCC was determined according to the Barcelona clinical liver cancer staging (BCLC stage).If it is stage B, the patient must be ineligible for surgery and/or local treatment, or develop disease following surgery and/or local treatment, or the patient rejects surgery and/or local treatment (must be specified and signed).
- 4. I have not received any systemic therapy for HCC (mainly including systemic chemotherapy, anti-vascular therapy, molecular targeted therapy and immunotherapy containing ctla-4, pd-1 / pd-l1 monoclonal antibody).
- 5. according to RECISTv1.1 criteria, there were ≥ 1 measurable lesion.Requirements: the selected target lesion had not received local treatment before, or the selected target lesion was located in the previously treated area, and was later confirmed as PD by imaging examination.
- 6. child-pugh liver function grade A, and no history of hepatic encephalopathy. 7. The ECOG (tumor cooperative group in the eastern United States) physical status score (PS) was 0 to 1.
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- 8. expected survival ≥12 weeks.
- 9. Major organ functions meet the following requirements: no blood transfusion, no use of hematopoietic stimulators (including g-csf, gm-csf, EPO and TPO) and infusion of human albumin preparations within 14 days prior to screening: neutrophil absolute count ≥1.5×109/L;Platelet count ≥ 80×109/L;Hemoglobin ≥ 90 g/L;Serum albumin ≥ 29 g/L;Total serum bilirubin ≤1.5× upper limit of normal range (ULN);Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 × ULN;Serum creatinine (Cr) ≤1.5×ULN or Cr clearance ≥40 mL/min (calculated by Cockcroft-Gault formula);International standardized ratio (INR) ≤2 or prothrombin time (PT) exceeding the upper limit of normal range ≤6 seconds;Urine protein \& lt;2+ (if urine protein ≥2+, 24-hour (h) urine protein quantification and 24h urine protein quantification should be performed \<1.0g can be enrolled).
- 10. if HBsAg(+) and/or HBcAb(+) are required, HBV DNA must \<500IU/mL (if the lower limit of the minimum detectable value of the local center is higher than 500IU/mL, after discussion with the sponsor, the enrollment can be decided according to the specific situation), and the patients should continue to receive the effective anti-hbv treatment that has been adopted or start to use entecavir or tenofovir throughout the study period. Co-infection with HBV and HCV was excluded. Patients with a history of HCV infection but negative PCR results for HCV RNA may be considered to be free of HCV infection.
- 11. Women of childbearing age must undergo a blood pregnancy test within the first 7 days of randomization with negative results and agree to use a reliable and effective method of contraception during the trial and within 60 days of the last trial drug administration. Male patients whose partners are women of childbearing age must agree to use a reliable and effective method of contraception during the trial and within 60 days of the last trial drug administration.
- 12. Patients voluntarily participated, fully informed consent, and signed written informed consent, with good compliance.
Who cannot join
- 1. known as cholangiocarcinoma (ICC) or mixed hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, and hepatic fibrolamellar carcinoma.
- 2. Had developed malignant tumor other than HCC within 2 to 5 years;However, limited tumors treated by the study were excluded, including carcinoma in situ of the cervix, basal cell carcinoma of the skin, and carcinoma in situ of the prostate.
- 3. had undergone liver surgery and/or local or experimental drug therapy for HCC in the first 4 weeks of randomization;Palliative radiotherapy for bone metastases was performed in the first 2 weeks of randomization.The toxic reaction (except hair loss) caused by previous treatment did not recover to ≤1 (nci-ctc AE v 5.0).Within 2 weeks prior to randomization, a Chinese medicine preparation with anti-hepatocellular carcinoma effect was received.
- 4. screening is not the control of pericardial effusion, uncontrolled pleural effusion or clinically significant moderate peritoneal effusion, defined as to the following criteria: screening, have clinical symptom and physical examination can detect the thoracic and abdominal cavity effusion or in the process of screening, need for thoracic and abdominal cavity effusion puncture pumping cavities or fluid and medication.
- 5. A history of gastrointestinal bleeding in the first 6 months;In patients with portal hypertension, the researchers concluded that patients with a high risk of bleeding (including moderate to severe esophageal and gastric varices at risk of bleeding, locally active gastrointestinal ulcers, and persistent positive fecal occult blood) should undergo gastroscopy to exclude patients with "red sign".If there is a "red sign" in the history of gastroscopy, it should be excluded from the group.
- 6. Present with grade ≥3 (nci-tc AE v5.0) gastrointestinal or non-gastrointestinal fistula.
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- 7. The main portal vein tumor thrombus (Vp4) or inferior vena cava tumor thrombus should be excluded.However, patients with a main portal vein tumor thrombus but unobstructed branches of the contralateral portal vein may be admitted.
- 8. Previous history of serious cardiovascular and cerebrovascular diseases: congestive heart failure, unstable angina, myocardial infarction or cerebrovascular accident stroke of New York cardiology association (NYHA) level II or above occurred in the 12 months before enrollment, or poorly controlled arrhythmias.Cardiac ultrasound examination of LVEF (left ventricular ejection fraction) \<50%.Corrected QT interval (QTc) \>480ms (calculated using the Fridericia method, if QTc is abnormal, it can be detected for 3 times at an interval of 2 minutes, and the average value is taken).High blood pressure (systolic blood pressure (BP) ≥150 mmHg and/or diastolic blood pressure ≥100mmHg) (mean of ≥3 BP readings based on ≥2 measurements) that are difficult to control with medication.Hypertensive crisis or hypertensive encephalopathy occurred in the past.
- 9. Significant bleeding disorder or other evidence of significant bleeding tendency: clinically significant hemoptysis or tumor bleeding of any cause occurred within 2 weeks prior to enrollment;Thrombosis or embolism events occurred within 6 months before enrollment;Anticoagulant therapy for therapeutic purposes (except low molecular weight heparin therapy) was used within 2 weeks prior to enrollment;Antiplatelet therapy is required.Current or recent (10 days before enrollment) use of aspirin (\>325 mg/d), clopidogrel (\>75 mg/d) or with dipyridamole, ticlopidine or cilostazol.Patients with metastatic lesions that invade the great vessels, respiratory tract, or mediastinum and are at significant risk of bleeding.
- 10. underwent major surgery in the first 4 weeks of randomization, but did not include diagnostic biopsies.
- 11. There have been CNS metastases 12. Severe unhealed wounds, active ulcers, and untreated fractures 13. Live vaccine was administered within 30 days prior to randomization. 14. An active autoimmune disease (i.e., immunoregulatory drugs, corticosteroids, or immunosuppressive drugs) requiring systemic treatment in the past 2 years;However, alternative therapy (such as thyroxine, insulin, or physiological corticosteroid replacement for adrenal or pituitary insufficiency) is not considered a systemic treatment and is permitted for use and inclusion.
- 15. A history of definite interstitial lung disease or non-infectious pneumonia, unless caused by local radiotherapy;A history of active tuberculosis.
- 16. Any severe acute or chronic infection requiring systemic antimicrobial, antifungal or antiviral treatment at the time of screening, excluding viral hepatitis.
- 17. A history of human immunodeficiency virus (HIV) infection is known. 18. Previous allogeneic stem cell or solid organ transplantation. 19. Inability to swallow tablets, malabsorption syndrome, or any condition that affects gastrointestinal absorption.
- 20. A history of severe allergy to any monoclonal antibody, anti-angiogenic target drug is known.
Trial locations and contacts
1 site in 1 country.
About this study
The aie of this clinical study is the safety and efficacy of combination therapy for HCC patients.
Read the detailed description
Activation of anti-tumor immune response using programmed death receptor-1 (PD-1)blockade showed benefit only in a fraction of hepatocellular carcinoma (HCC) patients. Specific blockade of vascular endothelial receptor 2 (VEGFR-2) using a murine antibody significantly delayed primary tumor growth but failed to prolong survival. Combining PD-1 blockade with antiangiogenesis has shown promise in substantially increasing the fraction of HCC patients who respond to treatment in vitro. Based on these clinical data, we are aimed to investigation the safety and efficacy of combination therapy for HCC patients.
- Being tested
- Bevacizumab Injection, Nivolumab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bevacizumab InjectionDrug
15mg/kg (Q3W)
NivolumabDrug
nivolumab 480 mg IV infusions for 30 minutes q4w
| Study group | Role | What they receive |
|---|---|---|
| Bevacizumab and anti-PD-1 therapy | Experimental | Not described Receives: Drug: Bevacizumab Injection; Drug: Nivolumab |
| Bevacizumab | Active comparator | Not described Receives: Drug: Bevacizumab Injection |
| anti-PD-1 | Active comparator | Not described Receives: Drug: Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
PFS
Mainly observe the PFS of HCC patients
Measured: 1.5 years
OS
Mainly observe the OS of HCC patients
Measured: 1.5 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 May 2020
- Study start11 May 2020
- Primary completion30 Jul 2021
- Study completion31 Aug 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Progress Free Survival (PFS) and Overall Survival (OS)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fuda Cancer Hospital, Guangzhou
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04393220
- Sponsor's protocol ID
- ML-20200511
- Status last verified
- Jun 2020
- First submitted
- 11 May 2020
- Last updated
- 5 Sep 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 5 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combination of PD-1 and VEGFR-2 Blockade for Advanced Hepatocellular Carcinoma
- ClinicalTrials.gov ID
- NCT04393220
- Acronym / sponsor ID
- ML-20200511
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Fuda Cancer Hospital, GuangzhouUniversity, hospital or other
- Study start
- 11 May 2020 (actual)
- Primary completion
- 30 Jul 2021 (actual)
- Study completion
- 31 Aug 2021 (actual)
- First posted
- 19 May 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aie of this clinical study is the safety and efficacy of combination therapy for HCC patients.
Detailed description
Activation of anti-tumor immune response using programmed death receptor-1 (PD-1)blockade showed benefit only in a fraction of hepatocellular carcinoma (HCC) patients. Specific blockade of vascular endothelial receptor 2 (VEGFR-2) using a murine antibody significantly delayed primary tumor growth but failed to prolong survival. Combining PD-1 blockade with antiangiogenesis has shown promise in substantially increasing the fraction of HCC patients who respond to treatment in vitro. Based on these clinical data, we are aimed to investigation the safety and efficacy of combination therapy for HCC patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Bevacizumab and anti-PD-1 therapy | Experimental | Drug: Bevacizumab Injection, Drug: Nivolumab |
| Bevacizumab | Active comparator | Drug: Bevacizumab Injection |
| anti-PD-1 | Active comparator | Drug: Nivolumab |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 1. Age 18-70 (inclusive), male and female
- 2. HCC was diagnosed by histopathological examination or the guidelines for the diagnosis and treatment of primary liver cancer (2017 edition).
- 3. Stage B (intermediate) or stage C (advanced) HCC was determined according to the Barcelona clinical liver cancer staging (BCLC stage).If it is stage B, the patient must be ineligible for surgery and/or local treatment, or develop disease following surgery and/or local treatment, or the patient rejects surgery and/or local treatment (must be specified and signed).
- 4. I have not received any systemic therapy for HCC (mainly including systemic chemotherapy, anti-vascular therapy, molecular targeted therapy and immunotherapy containing ctla-4, pd-1 / pd-l1 monoclonal antibody).
- 5. according to RECISTv1.1 criteria, there were ≥ 1 measurable lesion.Requirements: the selected target lesion had not received local treatment before, or the selected target lesion was located in the previously treated area, and was later confirmed as PD by imaging examination.
Key exclusion criteria (15 listed)
- 1. known as cholangiocarcinoma (ICC) or mixed hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, and hepatic fibrolamellar carcinoma.
- 2. Had developed malignant tumor other than HCC within 2 to 5 years;However, limited tumors treated by the study were excluded, including carcinoma in situ of the cervix, basal cell carcinoma of the skin, and carcinoma in situ of the prostate.
- 3. had undergone liver surgery and/or local or experimental drug therapy for HCC in the first 4 weeks of randomization;Palliative radiotherapy for bone metastases was performed in the first 2 weeks of randomization.The toxic reaction (except hair loss) caused by previous treatment did not recover to ≤1 (nci-ctc AE v 5.0).Within 2 weeks prior to randomization, a Chinese medicine preparation with anti-hepatocellular carcinoma effect was received.
- 4. screening is not the control of pericardial effusion, uncontrolled pleural effusion or clinically significant moderate peritoneal effusion, defined as to the following criteria: screening, have clinical symptom and physical examination can detect the thoracic and abdominal cavity effusion or in the process of screening, need for thoracic and abdominal cavity effusion puncture pumping cavities or fluid and medication.
- 5. A history of gastrointestinal bleeding in the first 6 months;In patients with portal hypertension, the researchers concluded that patients with a high risk of bleeding (including moderate to severe esophageal and gastric varices at risk of bleeding, locally active gastrointestinal ulcers, and persistent positive fecal occult blood) should undergo gastroscopy to exclude patients with "red sign".If there is a "red sign" in the history of gastroscopy, it should be excluded from the group.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bevacizumab Injection15mg/kg (Q3W) | Drug | Bevacizumab, Bevacizumab and anti-PD-1 therapy |
| Nivolumabnivolumab 480 mg IV infusions for 30 minutes q4w | Drug | Bevacizumab and anti-PD-1 therapy, anti-PD-1 |
Primary outcome
PFS
Time frame: 1.5 years
Mainly observe the PFS of HCC patients
OS
Time frame: 1.5 year
Mainly observe the OS of HCC patients
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Sep 2021.
- Individual participant dataSharing planned: Undecided
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bevacizumab Injection and Nivolumab in people with Progress Free Survival (PFS) and Overall Survival (OS), run by Fuda Cancer Hospital, Guangzhou at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
PFS (time frame: 1.5 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Sep 2021.